Investigation of the preventive effect of Sijunzi decoction on mitomycin C-induced immunotoxicity in rats by 1H NMR and MS-based untargeted metabolomic analysis

Abstract

Ethnopharmacological relevance: Sijunzi decoction (SJZD) is a well known traditional Chinese prescription used for the treatment of gastrointestinal disorders and immunity enhancement. It has been found to indeed improve life quality of chemotherapy patients and extensive used in clinical conbined with chemotherapeutics for the treatment of cancer.

Aim of the study: The aim of this study was to investigate the preventive effect of the immunotoxicity of SJZD on mitomycin C (MMC) and the metabolic mechanism of action.

Materials and methods: NMR and MS-based metabolomics approaches were combined for monitoring MMC-induced immunotoxicity and the protective effect of SJZD. Body weight change and mortality, histopathological observations and relative viscera weight determinations of spleen and thymus, sternum micronucleus assay and hematological analysis were used to confirm the immunotoxicity and attenuation effects. An OPLS-DA approach was used to screen potential biomarkers of immunotoxicity and the MetaboAnalyst and KEGG PATHWAY Database were used to investigate the metabolic pathways.

Results: 8 biomarkers in plasma samples, 19 in urine samples and 10 in spleen samples were identified as being primarily involved in amino acid metabolism, carbohydrate metabolism and lipid metabolism. The most critical pathway was alanine, aspartate and glutamate metabolism.

Conclusions: The variations in biomarkers revealed the preventive effect of the immunotoxicity of SJZD on MMC and significant for speculating the possible metabolic mechanism.

Keywords: (1)H NMR; 16-deoxyporicoic acid B (PubChem CID: 16736458); Immunotoxicity; MS; Metabolomics; Mitomycin C; Sijunzi decoction; atractylenolide I (PubChem CID: 5321018); atractylenolide II (PubChem CID: 14448070); atractylenolide III (PubChem CID: 155948); gancaonin I (PubChem CID: 480777); ginsenoside Re (PubChem CID: 441921); ginsenoside Rg(2) (PubChem CID: 75412551); liquiritigenin (PubChem CID: 114829); poricoic acid B (PubChem CID: 5471852).